Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarachnoid hemorrhage through a myeloid cell-dependent mechanism.
Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarachnoid hemorrhage through a myeloid cell-dependent mechanism.
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DOI：
10.1007/s12028-011-9651-3
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发表时间：
2012-04
影响因子：
3.5
通讯作者：
Provencio, J. Javier
中科院分区：
文献类型：
--
作者：
Smithason, Saksith;Moore, Shari Korday;Provencio, J. Javier
蛛网膜下腔出血（SAH）后迟发性恶化伴血管痉挛（DDAV）是发病的主要原因。我们先前已经证明，在小鼠模型中，在实验性SAH之前骨髓细胞耗竭改善DDAV。在这项研究中，我们解决是否脂多糖（LPS）的全身管理ADAV在骨髓细胞依赖的方式。我们在实验性SAH模型中，在出血前用LPS激发小鼠，并在第6天用印度墨水血管造影评估血管痉挛程度;通过旋转棒、Y-迷宫和巴恩斯迷宫测试评估行为缺陷;通过免疫组织化学评估SAH后早期小胶质细胞活化;以及血管痉挛时脑内趋化因子CCL 5和KC水平。另一组动物在LPS给药和SAH之前给予针对中性粒细胞抗原Ly 6 G/C的髓样细胞消耗抗体。SAH后的LPS可显著降低血管造影性血管痉挛以及巴恩斯迷宫测试成绩，但不能降低Y迷宫或旋转杆测试成绩。与单独SAH相比，SAH前LPS动物中小胶质细胞的活化增加。在LPS给药前耗尽骨髓细胞抑制了血管痉挛的发展，改善了行为测试的表现并减少了小胶质细胞的活化。趋化因子CCL 5和KC在SAH和LPS SAH中逐渐升高，但在骨髓细胞耗竭的动物中受到抑制。在SAH之前给予LPS通过骨髓细胞依赖性机制抑制DDAV，这支持了在人类中的研究，该研究表明全身性炎症增加了发展DDAV的可能性。
Delayed deterioration associated with vasospasm (DDAV) after aneurismal subarachnoid hemorrhage (SAH) is a major cause of morbidity. We have previously shown that myeloid cell depletion before experimental SAH in a murine model ameliorates DDAV. In this study, we address whether systemic administration of lipopolysaccharide (LPS) worsens DDAV in a myeloid cell-dependent fashion. We challenged mice in our experimental SAH model with LPS before hemorrhage and evaluated the degree of vasospasm on day 6 with India ink angiography; behavioral deficits by rotorod, Y-maze and Barnes maze testing; microglial activation early after SAH by immunohistochemistry; and the brain levels of the chemokines CCL5 and KC at the time of vasospasm. Another group of animals were given the myeloid cell-depleting antibody against the neutrophil antigen Ly6G/C prior to LPS administration and SAH. LPS followed by SAH significantly worsens angiographic vasospasm as well as performance on the Barnes maze but not the Y-maze or rotorod tests. There was an increased activation of microglia in animals with LPS before SAH compared to SAH alone. Depletion of myeloid cells before LPS administration inhibited the development of vasospasm, improved the performance on behavioral tests and reduced microglial activation. The chemokines CCL5 and KC were incrementally elevated in SAH and LPS SAH but suppressed in animals with myeloid cell depletion. LPS administration before SAH worsens DDAV through a myeloid cell-dependent mechanism supporting studies in humans which show that systemic inflammation increases the likelihood of developing DDAV.
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脑脊液中性粒细胞与蛛网膜下腔出血中血管痉挛的发生有关。
影响因子：
3.5
作者：
Provencio, J. J.;Fu, X.;Siu, A.;Rasmussen, P. A.;Hazen, S. L.;Ransohoff, R. M.
通讯作者：
Ransohoff, R. M.
影响因子：
4.8
作者：
Noble, Adam J.;Baisch, Stefanie;Schenk, Thomas
通讯作者：
Schenk, Thomas
影响因子：
8.3
作者：
Vergouwen, Mervyn D. I.;Ilodigwe, Don;Macdonald, R. Loch
通讯作者：
Macdonald, R. Loch
影响因子：
3
作者：
Altay, Tamer;Smithason, Saksith;Provencio, J. Javier
通讯作者：
Provencio, J. Javier
影响因子：
6.3
作者：
Etminan, Nima;Di Vergouwen, Mervyn;Macdonald, R. Loch
通讯作者：
Macdonald, R. Loch